Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracti...Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracting more and more attention from doctors and experts. However, little study has been done towards the effect of this approach for treating esophageal squamous cell carcinoma. This paper, therefore, intends to explore the possibilities of applying EGFR-TKI inhibitors or anti-EGFR monoclonal antibody in esophageal squamous cell carcinoma by studying the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Methods: Thirty-five cases of resected specimens of diagnosed esophageal squamous cell carcinoma with complete clinical and pathological data from January to April 2009 were collected. Pyrophosphate was used for observing the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Results: Examinations were undertaken respectively to the codon segment 746-754 of exon 19 in EGFR genes, codon 12 and 13 in K-ras genes as well as condon 600 in B-raf genes. No mutation was found in EGFR and B-raf genes with mutation rate 0% (0/35), all of codon 12 in K-ras genes were wild-type without any mutation, while 2 specimens of codon 13 had mutations with mutation rate of 5.71% (2/35). Conclusion: In treating esophageal squamous cell carcinoma patients, all K-ras genes are expressed as wild type due to low mutation rate; cetuximab is effective due to low mutation rate of B-raf while EGFR-TKI inhibitor will not be effective enough because of low mutation rate of EGFR genes.展开更多
L-type amino acid transporters(LATs) mainly assist the uptake of neutral amino acids into cells. Four LATs(LAT1, LAT2, LAT3 and LAT4) have so far been identified. LAT1(SLC7A5) has been attracting much attention in the...L-type amino acid transporters(LATs) mainly assist the uptake of neutral amino acids into cells. Four LATs(LAT1, LAT2, LAT3 and LAT4) have so far been identified. LAT1(SLC7A5) has been attracting much attention in the field of cancer research since it is commonly up-regulated in various cancers. Basic research has made it increasingly clear that LAT1 plays a predominant role in malignancy. The functional significance of LAT1 in cancer and the potential therapeutic application of the features of LAT1 to cancer management are described in this review.展开更多
Targeted drugs therapies that block the molecular pathways involved in the development and progression of gastro-intestinal(GI)cancers have recently gained considerable attention.In addition to agents targeting vascul...Targeted drugs therapies that block the molecular pathways involved in the development and progression of gastro-intestinal(GI)cancers have recently gained considerable attention.In addition to agents targeting vascular endothelial growth factor(VEGF),epidermal growth factor receptor,the multi-kinase inhibitor,and regorafenib have also become available for the treatment of metastatic colorectal cancer patients.Currently,trastuzumab,an antibody targeting human epidermal growth factor receptor-2(HER-2),in combination with cytotoxic drugs is considered as the standard treatment for patients with HER-2 positive gastric cancer(GC).The efficacy of ramucirumab,a human monoclonal antibody that inhibits VEGF from binding to its receptor in GC,has also been recently demonstrated.At present,a great number of novel targeted drugs are in pre-clinical or clinical studies.In this review,we summarize trends in the use of molecularly targeted drugs that have proven to be effective for treating GI cancers,with a focus on emerging strategies for personalized treatment.展开更多
Acute myeloid leukemia(AML)remains a most lethal hematological malignancy,partly because of its slow development of targeted therapies compared with other cancers.PLK1 inhibitor,volasertib(Vol),is among the few molecu...Acute myeloid leukemia(AML)remains a most lethal hematological malignancy,partly because of its slow development of targeted therapies compared with other cancers.PLK1 inhibitor,volasertib(Vol),is among the few molecular targeted drugs granted breakthrough therapy status for AML;however,its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits.Here,we report that transferrin-guided polymersomes(TPs)markedly augment the targetability,potency and safety of Vol to AML.Vol-loaded TPs(TPVol)with 4%trans-ferrin exhibited best cellular uptake,effective down-regulation of p-PLK1,p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells.Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow.The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood,bone marrow,liver and spleen,effectively enhanced mouse survival rate,and impeded bone loss.This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML.展开更多
The prognosis of metastatic disease of esophagogastric junction adenocarcinoma remains poor,despite using a variety of regimens using cytotoxic agents.Recent understanding of molecular characteristic and tumor microen...The prognosis of metastatic disease of esophagogastric junction adenocarcinoma remains poor,despite using a variety of regimens using cytotoxic agents.Recent understanding of molecular characteristic and tumor microenvironment of this cancer is currently instigating new therapeutic options.In this review,we summarized previous evidences of cytotoxic agents widely used worldwide,and updated recent developments of molecular targeted drugs,and immune checkpoint inhibitors.展开更多
文摘Objective: Molecular targeted drugs have been widely used in clinical application which has successfully prolonged some patients' life. Meanwhile, molecular targeted drug therapy for esophageal cancer are attracting more and more attention from doctors and experts. However, little study has been done towards the effect of this approach for treating esophageal squamous cell carcinoma. This paper, therefore, intends to explore the possibilities of applying EGFR-TKI inhibitors or anti-EGFR monoclonal antibody in esophageal squamous cell carcinoma by studying the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Methods: Thirty-five cases of resected specimens of diagnosed esophageal squamous cell carcinoma with complete clinical and pathological data from January to April 2009 were collected. Pyrophosphate was used for observing the mutations of EGFR, K-ras and B-raf in the esophageal squamous cell carcinoma tissues. Results: Examinations were undertaken respectively to the codon segment 746-754 of exon 19 in EGFR genes, codon 12 and 13 in K-ras genes as well as condon 600 in B-raf genes. No mutation was found in EGFR and B-raf genes with mutation rate 0% (0/35), all of codon 12 in K-ras genes were wild-type without any mutation, while 2 specimens of codon 13 had mutations with mutation rate of 5.71% (2/35). Conclusion: In treating esophageal squamous cell carcinoma patients, all K-ras genes are expressed as wild type due to low mutation rate; cetuximab is effective due to low mutation rate of B-raf while EGFR-TKI inhibitor will not be effective enough because of low mutation rate of EGFR genes.
文摘L-type amino acid transporters(LATs) mainly assist the uptake of neutral amino acids into cells. Four LATs(LAT1, LAT2, LAT3 and LAT4) have so far been identified. LAT1(SLC7A5) has been attracting much attention in the field of cancer research since it is commonly up-regulated in various cancers. Basic research has made it increasingly clear that LAT1 plays a predominant role in malignancy. The functional significance of LAT1 in cancer and the potential therapeutic application of the features of LAT1 to cancer management are described in this review.
文摘Targeted drugs therapies that block the molecular pathways involved in the development and progression of gastro-intestinal(GI)cancers have recently gained considerable attention.In addition to agents targeting vascular endothelial growth factor(VEGF),epidermal growth factor receptor,the multi-kinase inhibitor,and regorafenib have also become available for the treatment of metastatic colorectal cancer patients.Currently,trastuzumab,an antibody targeting human epidermal growth factor receptor-2(HER-2),in combination with cytotoxic drugs is considered as the standard treatment for patients with HER-2 positive gastric cancer(GC).The efficacy of ramucirumab,a human monoclonal antibody that inhibits VEGF from binding to its receptor in GC,has also been recently demonstrated.At present,a great number of novel targeted drugs are in pre-clinical or clinical studies.In this review,we summarize trends in the use of molecularly targeted drugs that have proven to be effective for treating GI cancers,with a focus on emerging strategies for personalized treatment.
基金National Natural Science Foundation of China(NSFC 52033006 and 82000157)Natural Science Foundation of Jiangsu Province(NO.BK20190173).
文摘Acute myeloid leukemia(AML)remains a most lethal hematological malignancy,partly because of its slow development of targeted therapies compared with other cancers.PLK1 inhibitor,volasertib(Vol),is among the few molecular targeted drugs granted breakthrough therapy status for AML;however,its fast clearance and dose-limiting toxicity greatly restrain its clinical benefits.Here,we report that transferrin-guided polymersomes(TPs)markedly augment the targetability,potency and safety of Vol to AML.Vol-loaded TPs(TPVol)with 4%trans-ferrin exhibited best cellular uptake,effective down-regulation of p-PLK1,p-PTEN and p-AKT and superior apoptotic activity to free Vol in MV-4-11 leukemic cells.Intravenous injection of TPVol gave 6-fold higher AUC than free Vol and notable accumulation in AML-residing bone marrow.The efficacy studies in orthotopic MV-4-11 leukemic model demonstrated that TPVol significantly reduced leukemic cell proportions in periphery blood,bone marrow,liver and spleen,effectively enhanced mouse survival rate,and impeded bone loss.This transferrin-guided nano-delivery of molecular targeted drugs appears to be an interesting strategy towards the development of novel treatments for AML.
文摘The prognosis of metastatic disease of esophagogastric junction adenocarcinoma remains poor,despite using a variety of regimens using cytotoxic agents.Recent understanding of molecular characteristic and tumor microenvironment of this cancer is currently instigating new therapeutic options.In this review,we summarized previous evidences of cytotoxic agents widely used worldwide,and updated recent developments of molecular targeted drugs,and immune checkpoint inhibitors.
